The time that blood spends in the pulmonary capillaries is a major determinant of the gas exchange effectiveness of the lungs. Consequently, physiologic mechanisms which alter this contact time may serve important regulatory functions. For example, during exercise some factors reduce contact time so that more red blood cells traverse the capillaries per unit time, thereby enhancing gas exchange. If, however, transit times become too rapid, arterial hypoxemia can result. The obvious importance of understanding how pulmonary microcirculatory hemodynamics are regulated have prompted numerous studies, but previous investigators have been forced to use indirect techniques and, in terms of red blood cell capillary transit time, to consider the lung as a single, homogeneous entity. In fact, it is likely that regional differences in pressure and flow within the lung give rise to regional differences in capillary transit. Using in vivo video fluorescence microscopy techniques recently developed by us, we propose to determine directly the length of time required for red blood cells to traverse pulmonary capillaries and to evaluate how transit time changes as a function of physiologic variables (pulmonary arterial and venous pressures, cardiac output, and pulmonary capillary recruitment). Specific emphasis is placed on studying mechanisms that reduce transit time in order to increase gas exchange. Finally, we will determine the site of sequestration and transit time of fluorescein labeled neutrophils when the cells are normal and activated.